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Review
. 2018 Jun 14;131(24):2621-2629.
doi: 10.1182/blood-2018-01-785840. Epub 2018 May 4.

Chimeric antigen receptor-modified T cells: CD19 and the road beyond

Alexander I Salter  1   2 , Margot J Pont  1 , Stanley R Riddell  1   2
Affiliations
Review

Chimeric antigen receptor-modified T cells: CD19 and the road beyond

Alexander I Salter et al. Blood. .

Abstract

The ability to harness a patient's immune system to target malignant cells is now transforming the treatment of many cancers, including hematologic malignancies. The adoptive transfer of T cells selected for tumor reactivity or engineered with natural or synthetic receptors has emerged as an effective modality, even for patients with tumors that are refractory to conventional therapies. The most notable example of adoptive cell therapy is with T cells engineered to express synthetic chimeric antigen receptors (CARs) that reprogram their specificity to target CD19. CAR T cells have shown remarkable antitumor activity in patients with refractory B-cell malignancies. Ongoing research is focused on understanding the mechanisms of incomplete tumor elimination, reducing toxicities, preventing antigen escape, and identifying suitable targets and strategies based on established and emerging principles of synthetic biology for extending this approach to other hematologic malignancies. This review will discuss the current status, challenges, and potential future applications of CAR T-cell therapy in hematologic malignancies.

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Conflict of interest statement

Conflict-of-interest disclosure: S.R.R. has stock or other ownership in Juno Therapeutics, has a consulting or advisory role for Juno Therapeutics, Cell Medica, and Adaptive Biotechnologies, and receives research funding from Juno Therapeutics. S.R.R. also holds patents on methods and composition of cell therapy. The remaining authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
CAR design. (A) Schematic of TCR and costimulatory molecule expression on T cells. (B-C) Synthetic single-chain receptors designed to deliver modified signal 1 and signal 2 in an scFv/CD28/CD3ζ (B) or scFv/4-1BB/CD3ζ format (C).
Figure 2.
Figure 2.
CAR toolbox. Toolbox of applications in synthetic biology that may extend and enhance the efficacy and safety of ACT.
See this image and copyright information in PMC

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